Organic triazinone compound



United States Patent 3,501,467 ORGANIC TRIAZINONE COMPOUND EdwardGritfin Shay, Belle Mead, and Sidney Cohen,

Hillsdale, N.J., assignors to Millmaster Onyx Corporation, New York,N.Y., a corporation of New York No Drawing. Original application Jan.18, 1965, Ser. No. 426,422, now Patent No. 3,437,419. Divided and thisapplication Mar. 26, 1968, Ser. No. 715,962 Int. Cl. C07d 55/14; D06m13/40 US. Cl. 260-248 8 Claims ABSTRACT OF THE DISCLOSURE The organictriazinone compound having the structure:

it HOCHr-N IIICHH Hz CH2 wherein R is a radical selected from the groupconsisting of aliphatic, alicyclic and aromatic radicals bearing theresidue of an acidic group, and Z is the cation of a micro'biologicallyactive quaternary ammonium salt.

This is a division of co-pending application Ser. No. 426,422, filedJan. 18, 1965, now U.S. Patent No. 3,437,419.

This invention relates to durable microbicidal agents for cloth, paperand other fabrics or the fibers from which they are constructed.

An object of the invention is to synthesize antimicrobial compounds of anature suitable for application to such materials.

Another object of the invention is to apply the said antimicrobialagents to the fibers in such manner as to fix them thereon so as toresist depletion of the said agents by repeated laundering ordry-cleaning.

A further object of the invention is to obtain fabrics or fibers whichare self-sanitizing; that is to say, which will prevent the propagationof microorganisms thereon, and which will kill microorganisms with whichthey may become contaminated by air-borne matter, or upon vbeing worn inthe form of garments, or by handling or by other means.

The agents with which the above objects can be accomplished are of theclass of thermosetting cyclic organic compounds of the triazinone type,containing as a part of their structure a germicidally potent quaternaryammonium salt of an integral acid group. These triazinones are derivedfrom 1,3-dimethylo1 tetrahydro-striazin-Z-one which contains in the Sposition a radical having a terminal acidic group.

They conform, in general, to the following structure:

HOCHFN/ wherein R is an aliphatic, alicyclic or aromatic radical bearingthe residue of an acidic group such as carboxylic, sulfonic, sulfuric,phosphoric and the like, and Z is the cation of a quaternary ammoniumsalt.

3,501,467 Patented Mar. 17, 1970 Triazinones are well known to the art,and may be prepared by reacting urea, an aldehyde and a primary amine. Atypical preparation is described in Self-Smoothing Fabrics, by J. T.Marsh, p. 77, (Chapman and Hall Ltd, 1962). Triazinones containing anacid radical have also been described, as well as their silver,mercurial and other metal salts.

Germicidal quaternary ammonium salts such as the halides have been foundto 'be substantive to cloth, and particularly to cellulosic fabrics,which are thereby rendered self-sanitizing. Ordinary laundering,however, removes the germicide in one or, at most, a very few washingswith either soap or synthetic detergents.

We have now found that we can render a fabric durably self-sanitizingand that this antibacterial effect persists after repeated launderings,by treating it with a quaternary triazinone compound having thestructure described above, and heating it in the presence of a suitableacidic catalyst to fix the triazinone to the cellulose by cross-linking.

Triazinone salts of this type may be prepared by heating urea andformaldehyde or other aldehyde with the alkali-metal salts of organicacids containing a' primary amino group such as glycine, aminobutyricacid, sulfanilic acid, aminobenzoicacid and the like. The correspondingmicrobicidal quaternary ammonium salts may then be prepared bymetathesis. Upon reacting them in solution with quaternary ammoniumhalides or other suitable salts, the quaternary ammonium triazinonesalts separate out as a liquid or a solid phase which can be thusisolated and, if desired, further purified; however, suchafter-treatment is usually unnecessary.

Alternatively, a quaternary ammonium hydroxide or salt may be reactedwith an amino-substituted acid or its alkali-metal salt to yield thequaternary ammonium amino-substituted organic salt which can besegregated as described in pending applications, Ser. Nos. 323,598 and357,281, filed on Nov. 12, 1963 and Apr. 3, 1964, respectively, now US.Patent No. 3,299,073 and 3,361,- 792, respectively. The resultant aminocompound may then be reacted with urea and formaldehyde to form thecorresponding substituted triazinone, or with dimethylol urea to formthe triazinone compound unsubstituted in the l,3-positions which maythen be further reacted with formaldehyde to form the 1,3-dimethyloltriazirione compound.

Typical examples of the quaternary ammonium compounds which may be usedin this invention are the alkyl trimethyl ammonium chlorides,alkyl-benzyl trimethyl ammonium chlorides, alkyl dimethyl benzylammonium chlorides, alkyl dimethyl menaphthyl ammonium chlorides, alkyldimethyl substituted-benzyl ammonium chlorides in which the benzylradical is substituted with one or more side chains containing from 1 to5 carbon atoms such, for example, as methyl, dimethyl, ethyl and thelike and in which the carbon atoms may all be in the same or dilferentside chains or in which the benzyl radical bears one, two or morehalogen atoms such as chlorine or bromine, alkyl pyridinium chlorides,alkyl isoquinolinium chlorides and bromides, alkyl lower-alkylpyrrolidinium chlorides, alkyl lower-alkyl morpholinium chlorides in allof which the alkyl group may have from 8 to 22 carbon atoms and thelower-alkyl group may have from 1 to 4 carbon atoms and alkyl phenoxyethoxy ethyl dimethyl benzyl ammonium chloride in which the alkylradical may be isO-octyl or nonyl and in which the phenyl radical may,if desired, be substituted by a methyl radical. Various other analogs ofthese quaternaries may also be employed such, for example, as cetyldimethyl ethyl ammonium bromide or oleyl dimethyl ethyl ammoniumbromide.

In general, the quaternary ammonium compounds useful in this inventionare the higher alkyl quaternary ammonium hydroxides, halides (chloridesand bromides),

sulfates, methosulfates and the like possessing the following formula:

where R is an alkyl or alkaralkyl radical containing from 8 to 22 carbonatoms or an alkyl phenoxy ethoxy ethyl radical in which R is an alkylradical containing from 8 to 9 carbon atoms and in which the phenylradical may be substituted by a methyl group; R and R" are methyl orethyl radicals or members of a heterocyclic ring system such aspyridine, isoquinoline, pyrrolidine and morpholine; R is a methylradical or a benzyl group or a substituted-benzyl group such, forexample, as a monochlorobenzyl radical or a dichlorobenzyl radical ormixture thereof or a methyl benzyl, dimethyl benzyl, ethyl benzyl,diethyl benzyl, isopropyl benzyl, tertiary butyl benzyl or anotherbenzyl radical containing from 1 to carbon atoms as side chains, eitheras a single side chain or a multiplicity of side chains includingmixtures thereof or a menaphthyl group or hydrogenated menaphthyl group.When R and R" are members of a morpholine or pyrrolidine ring, R" is amethyl, ethyl, propyl or butyl group. When R and R" are members of anunsaturated heterocyclic ring such as pyridine or isoquinoline, R'" isthe same radical as R". X in the above formula corresponds to a halideradical such as chloride, bromide or iodide or to any otherwater-soluble anion such as methosulfate.

In general, we prepare to use such quaternary ammonium compounds whichhave a phenol coeflicient of at least 100 with respect to bothStaphylococcus aureus and Asalmonella typhosa at 20 C. when determinedby the standard method given in the Official Methods of Analysis of theAssociation of Ofiicial Agricultural Chemists, ninth edition (1960), p.63 et seq.

The following examples of methods of preparing, applying and testing theintermediates and the products of this invention are illustrated only,and are not to be con sidered at limiting the invention.

EXAMPLE I One mol of urea was dissolved in 400 grams or 3.2 mols offormalin solution in a three-neck flask fitted with an agitator, areflux condenser and a dropping funnel. The temperature thereupon fellto 10 C. A solution of 75 grams of 0.6 mol of taurine (Z-aminoethanesulfonic acid), 60 grams of water and 48 grams or 0.6 mol of 50% sodiumhydroxide solution was charged into the dropping funnel, whence it wasadded gradually to the agitated urea-formaldehyde solution. Anexothermic reaction occurred. The reaction was continued for one hourunder reflux at about 95 C. until the reaction was essentially completeand the free formaldehyde content was less than 1%. The productcontained 0.6 mol of 1,3-dimethyloltetrahydro-S-(sodiumsulfoethyl)-s-triazine 2 one, at a concentration of about 35%. Aftercooling, the solution was clarified by filtration through paper.

EXAMPLE II The reaction according to Example I was carried out withoutexcess of urea and formaldehyde. A solution of sodium tauride wasprepared by dissolving 125 grams or 1 mol of 2-aminoethane sulfonic acidand 80 grams or 1 mol of 50% sodium hydroxide solution in 400 grams ofwater. This solution was added gradually to a solution of grams or 1 molof urea in 324 grams or 4 mols of formalin solution, with agitation, andat about 60 C. The reaction mixture was then heated at the refluxingtemperature for one hour until the free formaldehyde conv '4 I tent was1.45%. The product, 1,3-dimethylo1-tetrahydro- 5- (sodiumsulfoethyl)-s-triazin-2-one of molecular weight 291, was obtained in 30%concentration.

'EXAMPLE III By substituting 173 grams or 1 mol of sulfanilic acidforthe taurine of Example II, and conducting the reaction in a similarmanner until the residual formaldehyde content was 2.9%, a 30% solutionvof 1,3-dimethylol-tetra hydro-S-(sodium p-sulfophenyl)-s-triazin-2-oneof molecular weight 339 was obtained.

EXAMPLE IV A solution containing 1 mol of sodium m-aminobenzoate wasprepared by dissolving 137 grams of m-benzoic acid in 181 grams of waterand grams of 50% sodium hydroxide. This was reacted as in Example 11with 60 grams of urea and 324 grams of Formalin, representing 1 mol and4 mols respectively, until the residual formaldehyde assayed 2.6%. Thesolution was clarified by filtration and contained 40% of1,3-dimethylol-tetrahydro-5- (sodium m-carboxyphenyl)-s-triazin-2-one ofmolecular weight 303.

EXAMPLE V A 40% solution of 1,3-dimethylol-tetrahydro-5-(sodiumcarboxymethyl)-s-triazin-2-one of molecular weight 241 was prepared inthe manner of Example IV, substituting for the sodium aminobenzoate, 218grams'of a solution containing 1 mol of sodium aminoacetate. Thefiltered product contained 2.8% of unreacted formaldehyde.

EXAMPLE VI EXAMPLE VII Without further purification, the product ofExample VI was applied to 80 x 80 cotton print cloth test fabric asfollows: I

A 2% aqueous solution of the crude product of Example VI, containing0.2% by weight'of Onyx Chemical Corporations Catalyst ZM (a modifiedzinc nitrate catalyst containing 2 0% of zinc nitrateand an organicacid), was applied on a padder to about 75% wet pickup. This solutiontherefore contained 1% of the alkyl dimethyl ethyl-benzyl ammonium saltof the triazinone and 1% of the alkyl dimethyl ethyl-benzyl ammoniumchloride. For a control, the same test fabric was treated with a 1%solution of the alkyl dimethyl ethyl-benzyl ammonium chloride and 0.2%of'the Catalyst ZM, applied in the same manner. Both swatches were driedfor 2 minutes at 220 F. and cured for 5 minutes at 300 F.

They were then laundered in an automatic washing machine of thehousehold type at 140 F. with Tide (Tide is the registered trademark ofthe Procter and Gamble Company) and dried in a tumble drier. Thisprocess was repeated for ten successive launderings.

The two swatches, and also two corresponding-'unlaundered swatches, weretested bacteriologically as follows, according to Tentative Test MethodNo; -1961 T of the Technical-Manual of the American Association of .wereincubated at 37 C. for eighteen hours, after which the swatches wereshaken with sterile distilled water. The suspensions were dilutedserially and plated in tryptone glucose extract agar and incubated at 37C. for fortyeight hours. The percentage reduction of the inoculum wascalculated in the prescribed manner. A self-sanitizing activity claimcalls for a minimum reduction of 90% in the number of organisms whichwere inoculated.

Table I shows the number of organisms recovered; UCT=untreated controlfabric; A=unlaundered fabric treated with the product of Example VI andAW=the same after ten launderings; B=unlaundered fabric treated withalkyl dimethyl ethyl-benzyl ammonium chloride and BW=the same after tenlaunderings; TNC=too numerous to count.

TABLE I Percent Organisms Organisms Recovered Killed UCI 300x A 0 99. 99100 A 0 99. 99 100 AW 107Xl0 99. 950 AW x10 99. 901 B 0 09. 99 100 B 099. 99 100 BW TNC BW TN 0 EXAMPLE VIII 216 grams of the product ofExample III was reacted with an equimolar amount of a 10% solution ofthe alkyl dimethyl ethyl-benzyl ammonium chloride of Example VI. Thereaction mixture was transferred to a separatory funnel along with alittle benzene and the oily product layer was removed and dried in avacuum oven. The product, 1,3-dimethylol-tetrahydro S-(alkyl dimethylethyl-benzyl ammonium-p-sulfophenyl)-s-triazin-Z-one, was recovered in82% yield.

EXAMPLE IX 390 grams of the product of Example 11 was reacted with anequimolar amount of an aqueous solution of alkyl dimethyl benzylammonium chloride (Onyx Chemical Corporations BTC 824 in which the alkyldistribUtlOl'l IS C14, C15, C12, C13). The reaction mixture was shakenin a separatory funnel along with a small quantity of benzene and theorganic product layer was separated and vacuum dried. The product,l,3-dimethylol-tetrahydro S-(alkyl dimethyl benzyl ammoniumsulfoethyl)-s-triazin-2-one, was recovered in 85% of the theoreticalyield.

EXAMPLE X EXAMPLE X1 390 grams of the product of Example V was reactedwith an equimolar amount of a solution of the alkyl dimethyl benzylammonium chloride of Example IX. The reaction mixture was shaken in aseparatory funnel with a little benzene and the organic product layerwas removed and dried in a vacuum oven. The product,1,3-dimethylol-tetrahydro-S-(alkyl dimethyl benzyl ammoniumcarboxymethyl)-s-triazin-2-one, was recovered in 82% of the theoreticalyield.

The above examples demonstrate the preparation of triazinone compoundscontaining as an integral part of the molecule a microbicidally activequaternary ammonium group. They also demonstrate that these compounds,like the simpler triazinone compounds from which they are derived, canbe permanently affixed to fabrics and especially to cellulosic fabricsby cross-linking, thus rendering the fabrics self-sanitizing.Furthermore, they show that the germicidal properties of the fabricpersist after repeated launderings.

Fabrics and fibers thus self-sanitized may be employed for a number ofuseful purposes, such as the preservation of the fibers themselves fromdecay, the prevention of cross-infection and of airor dust-borneinfection, the inhibition of odor-forming bacteria and, in gen ral, thekilling or stasis of microorganisms which cause disease, putrefaction ordeterioration of materials. They find application in such articles asblankets, bedlinens, surgical dressings, hospital uniforms, air filters,curtains and draperies, upholstery stufiing and padding, diapers,undergarments, socks and the like.

The invention claimed is:

1. The organic triazinone compound having the struct-ure:

wherein R is either lower alkyl or phenyl which are terminallysubstituted by sulfuric acid or carboxylic acid groups, and Z is acation of a microbiologically active quaternary ammonium salt having aphenol coefficient of at least with respect to both Staphylococcusaureus and Salmonella typhosa at 20 C.

2. The compound of claim 1 wherein the anion is 1,3-dimethylol-tetrahydro-S-sulfoethyl-s-triazin-2-one.

3. The compound of claim 1 wherein the anion is 1,3-dimethylol-tetrahydro-5-sulfophenyl-s-triazin-Z-one.

4. The compound of claim 1 wherein the anion is 1,3-dimethylol-tetrahydro-S-m-carboxyphenyl-s-triazin-2-one.

5. The compound of claim 1 wherein the anion is 1,3-dimethylol-tetrahydro-5-carboxymethy1-s-triazin-2-one.

6. The compound of claim 1 wherein the cation is alkyl dimethylethylbenzyl ammonium.

7. The compound of claim 1 wherein the cation is alkyl dimethyl benzylammonium.

8. The compound of claim 1 wherein the cation is alkyl isoquinolinium.

References Cited UNITED STATES PATENTS 2,321,989 6/1943 Burke 260-248 XR3,067,062 12/1962 Etzel 260--248 XR HENRY R. JILES, Primary ExaminerJOHN M. FORD, Assistant Examiner US. Cl. X.R.

